SUMMARY OF WORK The ultimate goals of this project are to determine how arterial stiffness properties influence myocardial structure and function and contribute to cardiovascular morbidity and mortality. A. We have examined the contribution of arterial stiffness to left ventricular (LV)mass in 695 men and 616 women from Taiwan. In both sexes, the major predictors of LV mass were systolic blood pressure, body surface area and age; AGI ntributed minimally to LV mass in either sex. B. To determine whether growth hormone or sex steroid supplementation ameliorates arterial stiffness properties in older adults with deficiencies of these substances, we are measuring pulse wave velocity and AGI in men and women aged 65 years and older, before and after hormonal replacement. C. We are testing the hypothesis that 1-2 years of home-based aerobic exercise training can reduce arterial stiffness in the multicenter NIH-sponsored Activities Counseling Trial of 810 subjects 35-75 years old. D. To determine whether aerobic exercise training can reduce the elevated arterial stiffness of older heart failure patients, we will measure arterial stiffness and peak VO2 before and after a 3 month program of aerobic training. E. A multicenter study to determine whether arterial stiffness is an independent risk factor for cardiovascular events in elderly free- living persons has been initiated. F. Follow-up measurements of arterial stiffness on endurance trained older men and their sedentary age peers, initially studied in 1989-1991 have been obtained to determine whether chronic endurance training attenuates the normal age- associated increase in arterial stiffness. G. Arterial stiffness will be measured in the Pittsburgh, PA site for the Cardiovascular Health Study. Long-term follow-up of this cohort will allow us to examine the prognostic significance of arterial stiffness in an older population. H. The relationship between arterial stiffness and some newly discovered hormones involved in sodium and blood pressure regulation (plasma ouabain-like factor and marinobufagenin)is being examined in BLSA subjects across a large age and blood pressure range. I. We have recently discovered, in cross-sectionsl studies, estrogen replacement therapy (ERT) in postmenopausal women reduced BP and the age-associated increase in arterial stiffness and that the addition of progestins to ERT may reduce these beneficial effects. ERT has been found also to reduce longitudinal changes in SBP, even if ERT users presented higher Sbp levels than non-ERT users. The reduction of the longitudinal increase in SBP exerted by ERT was more pronounced in older postmenopausal women, and in those with lighter BMI. J. We are attempting to identify genetic factors contributing to exaggerated arterial stiffness and arterial intima -medial thickness in a Sardinian population (a founder population, relatively genetically homogenous compared to outbred populations) and to deterine whether these factors enhance the predictive accuracy for overall cardiovascular risk, when added to standard cardiovascular risk profile. - Human Subjects